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CHROMATINRE-MODELLING    Presented by:    Roll no. 10 : PragyeshDhungel    Roll no.21 : Nirjal Mainali    Roll no. 34 : Su...
Introduction   Gene Expression in Eukaryotes may include    Chromatin Remodelling as part of    transcriptional activatio...
Basic subunit of chromatin.i.e Nucleosome   Eukaryotic DNA is tightly packaged into repeated    structures known as nucle...
Basic Technique1. Remodeling: change in nucleosome  structure, but no change in position2. Sliding: displacing nucleosome ...
Two classes of chromatinremodeling enzymes  Two classes of enzymes that   regulate chromatin structure are:a)   Class I :...
Class I : Histone acetylase   Don’t alter nucleosome position   Covalent modification of histone proteins.   Includes h...
Regulation of histone acetylationin yeast
Class II : Chromatin remodelingfactors   It shifts nucleosome position with respect to    DNA, exposing regulatory sequen...
Chromatin remodelingis an active process   Chromatin remodeling factors use energy from    ATP hydrolysis to rearrange th...
Euchromatin                  (De-condensedheterochromatin   Chromatin)(condensedChromatin)
Classifying ChromatinRemodelers   Chromatin remodeling complexes are    classified based on protein motifs found in    ad...
SWI2/SNF2               ATPase     BROMO                subfamily                              ATPase   SANT              ...
Shared characteristics of chromatin remodelingComplexes :     • Bind   nucleosomes     • Are DNA-dependent ATPases     • R...
Role In Transcription:     eg. Nucleosome remodeling in     yeastSWI/SNFcomplexSAGAcomplex
DHS
Chromatin and cancer:   Cancer can occur when essential regulatory    proteins are altered such that development    stops...
Oncoprotein v-ErbA:   TR directs differentiation of chicken blood cells    by binding to thyroid hormone, through    targ...
AML and PML:   associated with chromosomal translocations.   In AML, gene that is disrupted encodes a    transcription f...
   Similarly in PML, retonic acid receptor(RAR)    (recruits histone deacetylase) binds to PML    and leads to to failure...
   in cell cycle controlling pathways also mutated    genes like   cyclin dependent kinase inhibitors(p16) and    retino...
References   http://www.nature.com/onc/journal/v20/n24/full/    1204322a.html   http://highered.mcgrawhill.com/sites/983...
Presentation  chromatin remodelling
Presentation  chromatin remodelling
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Presentation chromatin remodelling

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Presentation chromatin remodelling

  1. 1. CHROMATINRE-MODELLING Presented by: Roll no. 10 : PragyeshDhungel Roll no.21 : Nirjal Mainali Roll no. 34 : Sunil Timilsena
  2. 2. Introduction Gene Expression in Eukaryotes may include Chromatin Remodelling as part of transcriptional activation. Chromatin remodeling is the enzyme-assisted movement of nucleosomes on DNA.
  3. 3. Basic subunit of chromatin.i.e Nucleosome Eukaryotic DNA is tightly packaged into repeated structures known as nucleosomes. Individual nucleosomes consist of histone octamers with 146 (or 147) base pairs of double- helix DNA wrapped around it. Histone Protein can physically block interaction between Promoter DNA sequences and protein needed to initiate transcription. Chromatin rearrangement modifies the Histone- DNA structure so that transcription can occur.
  4. 4. Basic Technique1. Remodeling: change in nucleosome structure, but no change in position2. Sliding: displacing nucleosome along DNA3. Transfer: removing and transferring nucleosome to non-adjacent region of DNA
  5. 5. Two classes of chromatinremodeling enzymes Two classes of enzymes that regulate chromatin structure are:a) Class I : Histone acetylaseb) Class II : Chromatin remodeling factors
  6. 6. Class I : Histone acetylase Don’t alter nucleosome position Covalent modification of histone proteins. Includes histone tail modifications (Ac, Me, P, Ub, etc.) Proteins recruited by these modifications include: i)transcription factors ii)ATP-dependent nucleosomal remodeling enzymes iii)histone modifying enzymes
  7. 7. Regulation of histone acetylationin yeast
  8. 8. Class II : Chromatin remodelingfactors It shifts nucleosome position with respect to DNA, exposing regulatory sequences. These are often refered to as Swi/Snf factors because they were first identified as yeast mutants defective in mating type switching and in the ability to metabolize sucrose (sucrose non-fermenting).
  9. 9. Chromatin remodelingis an active process Chromatin remodeling factors use energy from ATP hydrolysis to rearrange the packing of nucleosomes in higher order chromatin structures. Remodeling improves access to DNA or histone binding sites recognized by transcriptional regulators or histone modifiers. Some of these bind to : i) Activation domains and de-condense the associated chromatin. ii) Repression domains and condense the associated chromatin.
  10. 10. Euchromatin (De-condensedheterochromatin Chromatin)(condensedChromatin)
  11. 11. Classifying ChromatinRemodelers Chromatin remodeling complexes are classified based on protein motifs found in addition to the ATPase domain, or on how the ATPase domain itself is structured. This classification is purely structural, designed to make it easier for us humans to sort them all out – it may not accord with functional criteria.
  12. 12. SWI2/SNF2 ATPase BROMO subfamily ATPase SANT ISWI subfamily SWI2/SNF2 ATPaseSUPERFAMILY ATPase CHD/Mi2 subfamily CHROMO DNA binding ATPase ATPase Ino80 subfamily
  13. 13. Shared characteristics of chromatin remodelingComplexes : • Bind nucleosomes • Are DNA-dependent ATPases • Recognize histone modifications • ATPase activity can be regulated • Interact with other proteins
  14. 14. Role In Transcription: eg. Nucleosome remodeling in yeastSWI/SNFcomplexSAGAcomplex
  15. 15. DHS
  16. 16. Chromatin and cancer: Cancer can occur when essential regulatory proteins are altered such that development stops but the cells can still divide. Examples: avian Erythroblast virus changing normal functional properties of thyroid hormone receptor(TR) by introducing oncoprotein v-ErbA. Acute myeloid leukemia(AML) and Promyelocytic leukemia(PML) in humans
  17. 17. Oncoprotein v-ErbA: TR directs differentiation of chicken blood cells by binding to thyroid hormone, through targeting of chromatin remodeling machinery including histone transferases. but v-ErbA, cant bind to thyroid hormone, so cant recruit histone transferases, instead recruits histone deacetylase to block specialized cell funtions, causing proliferation of cells leading to leukemia.
  18. 18. AML and PML: associated with chromosomal translocations. In AML, gene that is disrupted encodes a transcription factor AML-1, which controls myeloid specific gene expression. in chromosomal translocation, DNA binding domain of AML-1 binds with a protein ETO, that interacts with a histone deacetylase, that leads to repression of cell differentiation and leads to leukemia.
  19. 19.  Similarly in PML, retonic acid receptor(RAR) (recruits histone deacetylase) binds to PML and leads to to failure of myelocytes to differentiate and results leukemia. PML-RAR can bind with trans-retonoic acid which leads to conformational change to PML- RAR and release of histone deacetylase. This leads to remission of leukemia.
  20. 20.  in cell cycle controlling pathways also mutated genes like cyclin dependent kinase inhibitors(p16) and retinoblastoma(Rb) cause cancer. but if recognition and selective inhibition of these chromatin remodelling pathways can be done then cancer can be cured. thus this area has a wide scope in therapeutic and pharmaceutical industry.
  21. 21. References http://www.nature.com/onc/journal/v20/n24/full/ 1204322a.html http://highered.mcgrawhill.com/sites/98340923 39/student_view0/chapter10/chromatin_remod eling.html http://www.sabiosciences.com/pathway.php?s n=Chromatin_Remodeling http://www.sigmaaldrich.com/life-science/your- favorite-gene-search/pathway- overviews/chromatin-remodeling.html

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